Assessing a Subject&#39;s Circulatory System

ABSTRACT

An apparatus comprising: an input interface configured to provide signals from at least two sensors for at least two postures including: signals, dependent upon blood presence, from a first sensor when a subject is in a first posture; signals, dependent upon blood presence, from the first sensor when the subject is in a second posture; signals, dependent upon blood presence, from a second sensor when the subject is in the first posture; and signals, dependent upon blood presence. from the second sensor when the subject is in the second posture; and processing circuitry configured to determine and output a metric by combining, according to pre-defined calibration data the provided signals.

FIELD OF THE INVENTION

Embodiments of the present invention relate to assessing a subject'scirculatory system.

BACKGROUND TO THE INVENTION

The response of a subject's circulation system to a subject's posturechange may depend upon characteristics of the blood such as itsviscosity, characteristics of the circulation system such as itsresistance and how the autonomous nervous system responds to maintainhomeostasis.

Blood perfusion at a periphery may, for example, be dependent upon oneor a combination of the following factors:—

-   -   1. vascular disease such as for example Raynaud's disease    -   2. genetic problems such as for example scleroderma    -   3. an abnormal vaso-constriction or vaso-dilation response from        the autonomous nervous system instigated by for example diabetic        neuropathy or alcoholism    -   4. drug treatments such as for example Beta blockers    -   5. auto-immune diseases such as for example Lupus

It will therefore be appreciated that there may be many reasons why asubject's circulatory system response to a postural change may be“abnormal”. Different pathologies may have the same or different effectson circulation.

It would be desirable to provide an interim clinical indicator thatcharacterizes a response of the circulation system to a series ofpostural changes and provides a clinician with information which incombination with other information and the clinician's skill andknowledge may be used to assess whether or not pathology may be present.The medical practitioner can then, using his own medical knowledge,conduct independent investigations before identifying any pathology.

BRIEF DESCRIPTION OF VARIOUS EMBODIMENTS OF THE INVENTION

According to various, but not necessarily all, embodiments of theinvention there is provided an apparatus comprising:

an input interface configured to provide signals from at least twosensors for at least two postures including:

-   -   signals, dependent upon blood presence, from a first sensor when        a subject is in a first posture;    -   signals, dependent upon blood presence, from the first sensor        when the subject is in a second posture;    -   signals, dependent upon blood presence, from a second sensor        when the subject is in the first posture; and    -   signals, dependent upon blood presence. from the second sensor        when the subject is in the second posture; and        processing circuitry configured to determine and output a metric        by combining, according to pre-defined calibration data the        provided signals.

The signals, for each combination of sensor and posture, may comprisesat least one logarithm of detected light intensity.

The signals, for each combination of sensor and posture, may includeseparately a time varying component of detected light intensity and aquasi static component of detected light intensity.

The signals, for each combination of sensor and posture, may includeseparately a logarithm of a time varying component of detected lightintensity and a logarithm of a quasi static component of the detectedlight intensity.

The signals, for each combination of sensor and posture, may include asignal based upon a light intensity signal detected at an opticalreflectance sensor and a signal based upon a light intensity signaldetected at an optical transmission sensor.

The signals, for each combination of sensor and posture, may include asignal based upon a light intensity signal detected at a firstwavelength but not at a second wavelength and a signal based upon alight intensity signal detected at at least the second wavelength butnot the first wavelength.

The calibration data may be used to assess divergence of the providedsignals from an expected average of a statistical model of expectedsignals to produce the metric.

The calibration data may define a non-linear combination of the signals.

The calibration data may be predetermined using machine learning.

The apparatus may be configured to emulate an artificial neural networkcomprising a plurality of nodes each of which has associated weights forinputs to the node, wherein the calibration data provides said weights.

The apparatus may further comprise a memory storing multiple sets ofcalibration data comprising a set of calibration data for each of aplurality of predetermined standard sequences of different bodypostures.

At least one of the sensors may provide signals from optical reflectiondetectors.

A change from the first posture to the second posture may be expected tocause a local, as opposed to systemic, circulatory reaction

A change from the first posture to the second posture may cause, for thesubject, a relative vertical displacement with respect to the subject'sheart of a subject's peripheral limb without relative verticaldisplacement with respect to the subject's heart of the subject's head.At least the first sensor may be on the limb.

A change from the first posture to the second posture may be expected tocause a systemic circulatory reaction.

A change from the first posture to the second posture may cause, for thesubject, a relative vertical displacement with respect to the subject'sheart of the subject's head.

At least the first sensor may be on the subject's head. This firstsensor may provide signals from an optical transmission sensor.

The metric may record a divergence of the signals from an expectedpattern of signals that characterize an expected response of anormalized circulation system to the predetermined sequence of first andsecond postures.

A system may comprising: the apparatus and at least a first sensor and asecond sensor. The first sensor may be at a first location and thesecond sensor may be at a second, different, location. The first sensormay detect light at a first wavelength but not at a second wavelengthand the second sensor may detect light at the second wavelength but notat the first wavelength. The first sensor may be a reflectance sensorand may be attached without clamping using an opaque adhesive collarthat closely circumscribes the reflectance sensor. The first sensor andsecond sensor may be attached to a flexible substrate comprisinginterconnects that are connectable to the apparatus via an interface,wherein a portion of the flexible substrate, underlying one or more ofthe interconnects, has a manufactured structural weakness and wherein,in use, the portion of the flexible substrate having the structuralweakness connects with the interface which retains the substrate againstremoval such that on attempted removal of the flexible substrate fromthe interface the manufactured structural weakness breaks the one ormore interconnects. The interface may additionally detach a portion ofthe flexible substrate to reveal an indicator. The first sensor andsecond sensor may be attached to a flexible substrate for application toa subject and may be connectable to the processing circuitry via a firstset of interconnects embedded in the flexible substrate, wherein anordering of the interconnects embedded in the substrate is dependentupon whether the flexible substrate is for use on a right limb or a leftlimb and wherein the ordering of the interconnects embedded in thesubstrate, in use, is indicative to the processing circuitry of whetherthe flexible substrate is applied to a right limb of the subject or aleft limb of the subject. The first sensor and second sensor may beattached to a first side of a flexible reversible substrate and may beconnectable to the processing circuitry via a first set of interconnectson the first side of the flexible substrate and wherein a third sensorand a fourth sensor may be attached to a second side of the flexiblesubstrate and may be connectable to the processing circuitry via asecond set of interconnects on the second side of the flexiblesubstrate, wherein an ordering of the first set of interconnects acrossthe first side of the flexible interconnect, when the first side of theflexible substrate is upwards facing, is different to an ordering of thesecond set of interconnects across the first side of the flexiblesubstrate when the second side of the flexible substrate is upwardsfacing thereby enabling the processing circuitry to determine which sideof the reversible flexible substrate is operational. First signalsdetected by the first sensor may be processed to produce parallelsignals that have different frequency components before combination atthe processing circuitry and wherein second signals detected by thesecond sensor are processed to produce parallel signals that havedifferent frequency components before combination by the processingcircuitry.

According to various, but not necessarily all, embodiments of theinvention there is provided an apparatus comprising: a system forassessing a subject's blood circulation a first detector configured todetect signals dependent upon blood presence when the subject is in afirst posture and when the subject is in a second posture; at least oneother detector configured to detect signals dependent upon bloodpresence when the subject is in the first posture and when the subjectis in the second posture; and processing circuitry configured todetermine a metric by combining the detected signals from the first andsecond detectors for the first and second postures according tocalibration data.

According to various, but not necessarily all, embodiments of theinvention there is provided a method comprising: attaching opticalsensors to a subject; connecting the optical sensors to the apparatus;and moving the subject through a predetermined ordered sequence ofdifferent postures including the first and second postures. The opticalsensors may be attached by attaching a disposable flexible substrate tothe subject. The disposable flexible substrate may be attached to a limband may comprise at least one optical reflectance sensor. The flexiblesubstrate may be attached using adhesive only and without the use of aclamping force. The disposable flexible substrate may be attached to asubject's head and comprises at least one optical transmission sensor.

According to various, but not necessarily all, embodiments of theinvention there is provided an apparatus comprising: a methodcomprising: processing light intensity signals received from opticalsensors positioned on a subject when the subject is moved through apredetermined sequence of at least three different postures according toa kinematic protocol to provide input signals; combining the inputsignals to produce and output a metric that quantitatively defines aresponse of the subject's circulatory system to the predeterminedsequence of at least three different postures of the kinematic protocol.

According to various, but not necessarily all, embodiments of theinvention there is provided an apparatus comprising: a flexiblesubstrate; a first optical sensor at a first location on the flexiblesubstrate arranged in a reflectance configuration and

a first adhesive collar closely circumscribing the first optical sensor,a second optical sensor at a second location on the flexible substrate;anda second adhesive collar closely circumscribing the second opticalsensor, wherein the first adhesive collar is configured to position thefirst sensor adjacent a subject's body for physiological sensing andwherein the second adhesive collar is configured to position the secondsensor adjacent the subject's body for physiological sensing.

According to various, but not necessarily all, embodiments of theinvention there is provided an apparatus comprising: a flexiblesubstrate comprising a manufactured structural weakness; at least afirst sensor and a second sensor attached to the flexible substrate;interconnects connected to the first and second sensors; and aninterface for connecting the interconnects to a cable, wherein themanufactured structural weakness underlies one or more of theinterconnects adjacent the interface.

According to various, but not necessarily all, embodiments of theinvention there is provided an apparatus comprising: a reversibleflexible substrate having a first side and an opposing second side; afirst sensor and a second sensor attached to the first side of thereversible flexible substrate; a first set of interconnects, on thefirst side of the reversible flexible substrate, connected to the firstand second sensors in a first order; a third sensor and a fourth sensorattached to the first side of the reversible flexible substrate; asecond set of interconnects, on the second side of the reversibleflexible substrate, connected to the third and fourth sensors in asecond order; wherein the first order of the first set of interconnectsacross the first side of the flexible interconnect, when the first sideof the flexible substrate is upwards facing, is different to the secondorder of the second set of interconnects across the second side of theflexible substrate when the second side of the flexible substrate isupwards facing.

According to various, but not necessarily all, embodiments of theinvention there is provided an apparatus comprising: a flexiblesubstrate for application to a subject, the flexible substratecomprising at least a first sensor and a second sensor; a set ofinterconnects supported by the flexible substrate and connected to thesensors; an interface for connecting the interconnects to remoteprocessing circuitry; wherein an ordering of the interconnects isdependent upon whether the flexible substrate is for use on a right limbor a left limb and wherein the ordering of the interconnects isindicative, when the apparatus is in use, to the processing circuitry ofwhether the flexible substrate is applied to a right limb of the subjector a left limb of the subject.

According to various, but not necessarily all, embodiments of theinvention there is provided a collection of flexible substrates whereineach flexible substrate is ergonomically configured to be applied to adifferent body part of a subject, and comprises:

-   -   at least a first sensor and a second sensor;    -   a set of interconnects supported by the flexible substrate and        connected to the sensors;    -   an interface comprising a common fixed physical configuration of        interface connectors for connecting the interconnects to remote        processing circuitry;        wherein an ordering of the interconnects with respect to the        common fixed physical configuration of interface connectors is        dependent upon the body part to which a flexible substrate is to        be applied and wherein the ordering of the interconnects with        respect to the common fixed physical configuration of interface        connectors is uniquely indicative, when the flexible substrate        is in use, to the processing circuitry of the body part to which        the flexible substrate is attached.

According to various, but not necessarily all, embodiments of theinvention there is provided an apparatus comprising:

an input interface configured to provide signals dependent upon bloodpresence at at least two locations for at least two postures includingsignals dependent upon blood presence at a first location when a subjectis in a first posture, signals dependent upon blood presence at thefirst location when the subject is in a second posture, signalsdependent upon blood presence at a second location when the subject isin the first posture, and signals dependent upon blood presence at thesecond location when the subject is in the second posture;processing circuitry configured to determine and output a metric bycombining, according to pre-defined calibration data the providedsignals.

According to various, but not necessarily all, embodiments of theinvention there are provided methods, systems, apparatuses and computerprograms as claimed as the appended claims.

According to various, but not necessarily all, embodiments of theinvention there is provided a system and method for assessing asubject's circulatory system using optical sensors and multiple posturalchanges.

This provides the advantage of low cost, rapid pain free assessment ofsubject physiology by assessment of disturbances to the circulatorysystem.

It should therefore be appreciated that the present invention does notdiagnose a disease but provides an interim clinical indicator which isof a type that is not dissimilar to body temperature, blood pressure,heart rate etc.

BRIEF DESCRIPTION OF THE DRAWINGS

For a better understanding of various examples of embodiments of thepresent invention reference will now be made by way of example only tothe accompanying drawings in which:

FIG. 1 schematically illustrates a system comprising: optical sensorsand an apparatus;

FIG. 2 illustrates the apparatus in more detail;

FIG. 3 schematically illustrates an artificial neural network forproducing a metric;

FIGS. 4A and 4B illustrate different implementations of a flexiblesubstrate for sensors:

FIGS. 5A, 5B and 5C schematically illustrate safety features forflexible substrates.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS OF THE INVENTION

Functional tests are used to provoke changes in the circulatory systemof a subject. Functional test involves placing the subject intodifferent postures and recording data at those postures. The exactnumber, type, order, frequency of postures used in a particularfunctional test protocol is predetermined and depends upon the subject'sphysiology and pathology under investigation.

A kinematic protocol (or test) is a sequence of three or more differentpostures. The sequence is typically carried out in a single continuoussession. The sequence may be carried out as an uninterrupted sequencethat does not have significant hiatus between postural changes.

The different postures adopted during a kinematic protocol may forexample include at least three of: a reference posture, none, one ormore ‘local’ (or ‘limb’) postures, none, one or more ‘orthostatic’ (or‘torso’) postures, and none, one or more ‘systemic’ (or ‘whole body’)postures.

In a ‘local’ (or ‘limb’) posture, a limb has been moved through agravitational field relative to a stationary body torso.

In a ‘orthostatic’ (or ‘torso’) posture, the body torso has been movedthrough a gravitational field relative to a stationary limb or limbs(e.g. legs).

In a ‘systemic’ (or ‘whole body’) posture, the whole body has been movedwithin a gravitational field but without relative movement between thebody torso and limbs. This may be achieved by inclining a stationarysubject.

The at least three different postures result in at least two differentpostural changes. The postural changes are changes of the whole or partsof the body relative to a gravitational field. The different posturalchanges therefore result in different ‘impulses’ to the subject'scirculatory system.

It may be desirable to have a first type of impulse such as a ‘local’(or ‘limb’) impulse by changing to a ‘local’ (or ‘limb’) posture or an‘orthostatic’ (or ‘torso’) impulse by changing to an ‘orthostatic’ (or‘torso’) posture or a ‘systemic’ (or ‘whole body’) impulse by changingto a ‘systemic’ (or ‘whole body’) position. It may be desirable to alsohave a different second type of impulse. Therefore if the first type ofimpulse was ‘local’ (or ‘limb’) the second type of impulse may be‘orthostatic’ (or ‘torso’) or ‘systemic’ (or ‘whole body’) but not‘local’ (or ‘limb’).

The following kinematic protocol can be used to assess a local responseof a capillary bed i.e. vaso-dilation and vaso-contraction. A localpostural change is followed by a systemic postural change.

First the local postural change is performed. An initial referenceposture in which a subject is supine and an arm is level with the heartmay be followed by a local posture in which the subject is supine andthe arm is vertically displaced below the heart.

Then a systemic postural change is performed. An initial referenceposture in which a subject is supine and an arm is level with the heartmay be followed by a systemic posture in which the angle of incline ofthe body is changed without independent movement of the arm relative tothe torso so that the head is vertically displaced below the heart.

A sensor may be located on an index finger of the arm. This sensor maybe an optical transmission sensor which is sensitive to the arterialblood volume.

A sensor may be located on the forearm or the back of the hand. Thissensor may be an optical reflection sensor which is sensitive to skinvenous blood volume changes. The skin reflection sensor also permitsnormalizing of the digit transmission sensor caused by venous bloodvolume changes.

The outputs from the sensors have characteristics that produce differentpatterns as the kinematic protocol is performed. The patterns for anormal circulatory response share a common distinctive pattern. Thisdistinctive pattern may be determined theoretically or empirically andthen used to pattern match the outputs from the sensors for a subjectduring the same kinematic test. A metric may be output that indicateswhether or the degree of pattern matching. A pattern match indicates anormal circulatory response for the given kinematic test. A patternmismatch indicates an abnormal circulatory response that merits furtherinvestigation.

The following kinematic protocol can be used to assess arterial bloodsupply to the brain. An orthostatic (or body) postural change isfollowed by a systemic postural change.

First the orthostatic (or body) postural change is performed. Thesubject is initially in a supine reference position to record abaseline. The subject sits up or is sat up to an orthostatic (or body)posture, which would cause blood flow to the brain to initially reducedue to orthostatic pressure changes.

Then the systemic postural change is performed. The subject is returnedto the supine reference position to record a baseline. The subject inthe supine position is tilted so that the angle of incline of the bodyis changed so that the head is vertically displaced below the heart.

A sensor may be located on the subject's forehead. This sensor may be anoptical reflection sensor which is sensitive to localized venous bloodvolume caused by pooling.

A sensor may be located across the nose. This sensor may be an opticaltransmission sensor which is sensitive to the arterial blood volumewhich is dependent upon the interior carotid artery via the ophthalmicand ethmoidal arteries.

A sensor may be located on an ear lobe. This sensor may be an opticaltransmission sensor which is sensitive to the arterial blood volumewhich is dependent on the external carotid artery via the temporalartery.

The sensors are preferably at approximately the same height to avoidorthostatic compensation.

The outputs from the sensors have characteristics that produce differentpatterns as the kinematic test is performed. The patterns for a normalcirculatory response share a common distinctive pattern. Thisdistinctive pattern may be determined theoretically or empirically andthen used to pattern match the outputs from the sensors for a subjectduring the same kinematic test. A metric may be output that indicateswhether or the degree of pattern matching. A pattern match indicates anormal circulatory response. A pattern mismatch indicates an abnormalcirculatory response that merits further investigation such as aMagnetic Resonance Imaging (MRI) Scan if compromised blood supply to thebrain is a possibility.

FIG. 1 schematically illustrates a system 10 comprising: optical sensors2A, 2B, 2C and an apparatus 20.

The sensors 2A, 2B and 2C are positioned at respective locations 4A, 4B,4C of a subject's body. In the example illustrated, the sensors 2A and2B are attached to a substrate 6 and the substrate 6 is attached to thesubject's body 8.

The sensors are non-invasive sensors typically photo sensors such asoptical transmission sensors and/or optical reflection sensors. Thesensors are for sensing physiological attributes such as, for example,changes in the volume of the body (plethysmography). An optical sensorcomprises a light emitter and photo-detector. In a transmission sensor,in use, the photo-detector is positioned to receive light from the lightemitter that has passed through the subject's body 8. In a reflectionsensor, in use, the photo-detector is positioned to receive light fromthe light emitter that has been reflected by the subject's body 8.

It should be appreciated that the sensors 2A, 2B provide inputs to theapparatus 20 throughout the kinematic protocol i.e., for each posture ofthe subject.

Although only a single sensor is illustrated at each location, it shouldbe appreciated that multiple sensors may be implemented at eachlocation. For example, combinations of reflectance and transmissionsensors may be provided in the same location. Also sensors that operateat different wavelengths of light may also be positioned at the samelocation. A sensor operating in near infrared of around 850 nm would beweakly affected by absorption in tissue but strongly affected byabsorption by blood and could for example be used to monitor thereaction of a capillary bed during a kinematic test. Whereas a sensoroperating around 650 nm would be strongly affected by absorption intissue and could for example be used to monitor the reaction of skintone during a kinematic test. The signal from the 850 nm sensor wouldhave a much larger arterial component than the 650 nm sensor as it wouldpenetrate deeper into tissue.

The sensors communicate with the apparatus 20 either using wirelessmethods (ZigBee, Bluetooth, UHF radio etc) or cables.

The apparatus 20 comprises an input interface 22 that pre-processessignals received from the sensors 2A, 2C and provides signal 23 toprocessing circuitry 24. The processing circuitry 23 is configured todetermine and output a metric 25 by combining, according to pre-definedcalibration data 28 the provided signals 23.

In the example illustrated, the provided signals 23 dependent upon bloodpresence at a first, second and third locations 4A, 4B, 4C when asubject is in the different postures of the kinematic protocol.

The interface 22 may also perform some signal processing beforeproviding the signals 23 to the processing circuitry 24.

For example, the interface may separate an intensity signal from asensor into two distinct signals having different frequency components.For example, it may produce an ‘ac signal’ that relates to the timevarying intensity recorded at a sensor and a ‘dc signal’ that measuresthe quasi-static intensity recorded at the sensor.

As another example, the interface 22 may apply a non-linear functionsuch as a logarithmic function to the signals 23 before they areprovided to the processing circuitry 24.

The processing circuitry 24 may be implemented in any suitable manner.It may, for example, be a programmable computer or dedicated hardware.The interface 22 may be implemented in any suitable manner. It may, forexample, comprise a programmable computer or dedicated hardware.

It should be appreciated that the interface 22 and processing circuitrymay not be discrete physical components but may be functional modulesimplemented by common circuitry such as a processor executing differentsoftware modules.

The calibration data 28 is used to assess divergence of the providedsignals 23 from an expected pattern of signals that characterize anexpected response of a normalized circulation system to the kinematicprotocol. The expected response may be an average of a statistical modelof expected signals produced for example using machine learning.

The calibration data defines a non-linear combination of the signals.There will typically be different non-linear combinations of the signals23 required for different kinematic tests as any pattern to be matchedwill vary with the location and type of sensors used and with thekinematic test performed. There will therefore be different calibrationdata 28 for each kinematic test.

Referring to FIG. 2, the interface 22 comprises interface components 22Aetc for one of the sensors 2A, however only the interface component 22Afor the sensor 2A is illustrated. It should be appreciated that therewill be an equivalent interface component.

The interface component 22A comprises analogue front end signalprocessing circuitry 32 for processing the intensity signal receivedfrom the sensor 2A and at least one Analogue to Digital converter 34.

There may be multiple front ends intended for simultaneous continuousmonitoring of multiple sensors, or a single front end with anappropriate multiplexor switch. The front end circuitry may provide forconstant control of the current provided to the sensors, trans-impedanceamplification of the received signals 30, compensation for ambient lightinterference. This may be achieved using time division multiplexing(TDM), in which the periods where a light source is not illuminated,allows monitoring of ambient light interference. This may alternativelybe achieved using frequency division implemented by employing amodulated light source and a frequency locking or demodulation system.

The front end circuitry 32 may initialize the sensors by configuringitself for a mid-scale value of the semi-static signal component byvarying the LED intensity so the resultant signal would be mid waybetween a desired range, again for example unity. Any signal increasesor decreases would be accommodated within the signal ranges, reducingthe likelihood of signal saturation or diminishment.

In the example illustrated, the interface component 22A separates thereceived signal 30, after pre-processing, into two distinct signals 35,36 having different frequency components.

It may produce an ac signal 36 by passing the received signal 32 througha high pass filter 38. The ac signal 36 relates to the time varyingintensity recorded at a sensor. It may also produce a dc signal 35 bypassing the received signal 32 through a low pass filter 42 thatintegrates, typically with a time constant of several seconds. The dcsignal 35 relates to a quasi-static intensity recorded at the sensor.Filtering could be performed either in hardware using conventionallinear time invariant filters or after digitization within amicroprocessor using digital filters such as Finite impulse responsedesigns. Digital filtering has the advantage of being able to change thefilter parameters via software update if required.

The signal or signals (if high and low pass filtering has occurred)would then be fed to an analogue to digital converter (ADC) 35 beforebeing provided to the processing circuitry 24. The ADC may be a discreteitem or may be contained in a microprocessor.

A logarithmic function may be applied to signals before they areprocessed by the processing circuitry 24 to produce the metric 25. Thislogarithmic function may be applied in the analogue or digital domain.If applied in the digital domain, it may be applied by the interface 22or the processing circuitry 24.

Optical absorption spectroscopy can be modeled using the Lambert-BeerLaw, in which received optical intensity is proportional to anexponential function that has as its argument the product of a onedimensional optical path length and an absorption coefficient. Takingthe natural logarithm of the received intensity produces a result thatis linear in the optical path length. The optical path length may beassumed to vary depending on tissue blood volume, which is affected byposture and arterial dilation responses.

The processing circuitry in the illustrated example comprises aprocessor 40, a memory 42, a display 44 and a network interface 46. Theprocessor 40 is configured to read from and write to the memory 42, toprovide output commands to the display 44 and to communicate using thenetwork interface 46.

The processor 40 would typically execute a program 48 from a memory 42to calculate a metric 25 and then display the metric 25 on display 44.

The computer program may arrive at the apparatus via any suitabledelivery mechanism. The delivery mechanism may be, for example, acomputer-readable storage medium, a computer program product, a memorydevice, a record medium such as a CD-ROM or DVD, an article ofmanufacture that tangibly embodies the computer program. The deliverymechanism may be a signal configured to reliably transfer the computerprogram.

The exact form of the algorithm for a multi sensor, multi posturekinematic test is typically a summation of non-linear weighted inputsignals S 23. Some statistical manipulation may occur on the signals 23before input to the algorithm. For example the median of a dc signal 35may be calculated whereas a root mean squared value may be calculatedfor the ac signal 36.

The algorithm weights may be set using a-priori knowledge, or trainingusing a teaching pattern and altering the weights according to theerror.

If there are multiple postures i, multiple sensor sites j and multiplesensor wavelengths k at each sensor site, then the metric y could bedefined as:

$y = {\sum\limits_{k}{\sum\limits_{j}{\sum\limits_{i}{c_{ijk}\log \; s_{ijk}}}}}$

where S_(ijk) is the input signal 23 for posture i, at site j forwavelength k.

Calculation of the weights c is possible using regression analysis. Amulti posture kinematic test would be performed on a range of subjectswho would also undergo independent clinical assessment. Then a leastsquares regression analysis of the recorded inputs against an idealizedmetric permits the algorithm weights to be defined.

Alternatively the metric could be defined as an arbitrary weightedsummation of non-linear functions of the input signals S_(ijk) using anartificial neural network 50 such as, for example, schematicallyillustrated in FIG. 3.

Artificial Neural Networks (ANN) are a class of non-linear weightingalgorithms. The feed forward representation as illustrated in FIG. 3consists of a directed acyclic graph of interconnected nodes 52 arrangedin layers 54A, 54B, 54C.

The feed forward network 50 illustrated in FIG. 3 with three layers ofneurons. Each input signal 23A, 238, 23C, 23D is sent to every neuron 52in an input layer 54A. Each neuron 52 in the input layer 54A forms itsown weighted sum of its inputs 23A-D and provides the sum as an output.Each neuron 52 in the input layer 54A has its output connected to everyneuron 52 in a hidden layer 54B. Each neuron 52 in the hidden layer 54Bforms its own weighted sum of its inputs and provides the sum as anoutput. Each neuron 52 in the hidden layer 54B has its output connectedto every neuron 52 in an output layer 54C. Each neuron 52 in the outputlayer 54C forms its own weighted sum of its inputs and multiplies theweighted sum by an activation function to produce the metric 25.

The metric 25 may be constrained to be a continuous value between 0 and1 using a sigmoid function as the activation function, or between −1 and1 using a hyperbolic tangent (Tan h) function as the activationfunction. If the metric is to be discrete, then a signum or stepfunction could be used as the activation function.

In some implementations two layers 54 of neurons 52 may suffice.

The various weights applied in the weighted summations may be determinedusing supervised learning and back propagation. Alternatively optimumweights may be found using a genetic algorithm. The weights arecomprised in the calibration data 28.

If there are i input nodes, j hidden nodes and only a single outputnode, the metric may be defined as

${f\left( x_{i} \right)} = {f{\sum\limits_{j}{w_{g_{1\mspace{14mu} \ldots \mspace{14mu} j}}\left( {g_{v_{j}}{\sum\limits_{i}{w_{h_{1\mspace{14mu} \ldots \mspace{14mu} i}}\left( {h_{v_{i}}{\sum\limits_{i}{w_{i}x_{i}}}} \right)}}} \right)}}}$

Wherein h_(v) _(i) , g_(v) _(i) , x_(i) are:—

g _(v) _(i) =(g ₁ ,g ₂ , . . . ,g _(j)), h _(v) _(i) =(h ₁ ,h ₂ , . . .,h _(i)),

x _(i)(AC(λ_(1 . . . n) ,P _(1 . . . q))_(S) ₁ , DC(λ_(1 . . . n) ,P_(1 . . . q))_(S) ₁ , . . . , AC(λ_(1 . . . n) ,P _(1 . . . q))_(S) _(m), DC(λ_(1 . . . n) ,P _(1 . . . q))_(S) _(m) )

Note that x_(i) represents a vector of statistic for the correspondingSensor (S_(1 . . . m)) pulsatile component (AC) and quasi-static (DC)signal components for the different wavelengths (λ_(1 . . . n)) for eachposture (P_(1 . . . q)).

The weights are defined using a training algorithm. Training, like inthe simple algorithm above, requires known training data to be fed tothe ANN, and the weights are modified using an error function orlearning rule.

The network 50 would be trained by providing it with the input signalvalues for the postures obtained from a kinematic test and then matchingusing back propagation would be used to reduce an error between theoutput metric and an expected metric.

The steps for back propagation of ANN supervised learning may include:—

-   -   1. Present known training inputs to the ANN.    -   2. For each output neuron in the output layer, compare the ANN        output metric to the expected metric for that known training        sample and calculate the local error.    -   3. For each output neuron adjust the weights to lower the local        error.    -   4. Assign different contributions for the local error to the        neurons in the hidden layer, giving greater responsibility to        neurons connected by stronger weights.    -   5. Repeat the steps 3 and 4 for the neurons in the hidden layer        using each one's responsibility as its error.

It will be appreciated from the above that the metric is sensitive tothe location of a sensor and the order and nature of the postures in akinematic test.

To enable the correct order and nature of the postures to be performedfor a kinematic test corresponding to the current calibration data 28,the apparatus 20 may give instructions either via a display 44 or bysynthesizing a voice. The instructions would indicate when and how aposture of a subject should be changed.

There will be different sets of calibration data for different kinematictests. A menu may be provided to select a particular test. The correctcalibration data 28 would then be loaded for use by the apparatus 20along with the instructions telling the operative how to perform thekinematic test.

It is also important that the sensors are located accurately and appliedto a subject in a manner that does not arbitrarily interfere with thesignals 23.

FIGS. 4A and 4B illustrate two different examples of apparatus 60 havingflexible substrates 62 that are suitable for applying sensors to asubject 8.

The apparatus 60 illustrated comprises an ergonomically shaped flexiblesubstrate 62.

At one end 64 of the flexible substrate 62 are located light emitter(s)and photo-detector(s) in an adjacent configuration in order to act as areflection sensor 66.

An adhesive collar 68 that surrounds and closely circumscribes thereflectance sensor 66 is used to attach the end 64 of the flexiblesubstrate 62 to the subject. The collar 68 is preferably substantiallyopaque at the wavelengths at which the photo-detector operates so thatit acts to isolate the photo-detector from ambient light. The adhesivecollar may be shaped like an annulus. The adhesive collar 68 may beformed from hydrogel.

A second portion 70 of the flexible substrate 62 is folded to act as atransmission sensor 72—a light emitter(s) 72A is applied to one side ofa protuberance and a photo-detector(s) 72B is applied on the other sideof the protuberance.

An adhesive collar 68 that surrounds and closely circumscribes the lightemitter 72A and an adhesive collar 68 that surrounds and closelycircumscribes the photo-detector 72B are used to attach the end 70 ofthe flexible substrate 62 to the subject. The adhesive collarcircumscribes in the sense that it surrounds but it does not necessarilytouch. The collars 68 are preferably substantially opaque at thewavelengths at which the photo-detector operates so that it acts toisolate the photo-detector from ambient light. The adhesive collar maybe shaped like an annulus. The adhesive collar 68 may be formed fromhydrogel.

The adhesive collars 68 adhere sensors in the correct strategic placeand they avoid the use of a mechanical clip system, which would compressthe arteries and veins in the bridge of the nose. This is especiallyimportant for reflectance sensors as they are sensitive to avasodilatory response that would be masked by mechanical compression.

Conductive interconnects feed from an edge connector 74 (where theembedded contacts are exposed from within the flexible substrate and areinserted into a spring leaf type metal contact, one for each connector)to the ends 64, 70 of the flexible substrate 62, communicating with thelight sources and photo-detectors.

Referring to FIG. 4A the flexible substrate 62 has a ‘Y’ or ‘T’ shape.The end 62 is located at the forehead of the subject. The end 70 isfolded over the bridge of the nose to act as a transmission sensor.

The distance between the bridge of the nose and the reflection sensor onthe head may be adjusted using a buckle (not shown), typically locatedbetween the eye brows which is only possible using a flexible substratethat will conform around the buckle. Alternatively the flexiblesubstrate may be allowed to arch in order to accommodate excess length,as the hydrogel annulus adhesive should firmly affix the activecomponents of the non-invasive optical sensors against the skin. Theflexible substrate would typically be disposed of after use on a singlesubject to maintain hygiene and avoid subject cross contamination.

Referring to FIG. 4B the flexible substrate 62 has a ‘Y’ or ‘ T’ shape.The end 62 is located over the extensor digitorum brevis muscle, locatedover the region of the third cuneiform, cuboid and metatarsal bones ofthe foot. The end 70 of the substrate 62 would wrap over the end of thelocating toe (typically second toe). The transmission light emitter 72Ais applied to the nail matrix and the transmission photo-sensor 72B isapplied to the pad of the second toe, diametrically opposite the emitter72A.

During application of the sensor to the subject, the flexible substrateis designed to conform to the subject's foot, naturally following thecontours of the foot in order to locate over the second toe. Theflexible substrate is shaped to follow the curvature of the foot,approximating a ‘Z’ shape which is easily achieved by stamping andlaminating in conductive elements.

The advantages of the adhesive fixation method are that hydrogeladhesion locates the sensors in the correct strategic places on the footrather than using mechanical clip systems or loops around the diameterof the toe. The arteries feeding the pulp of the toe pass alongside theside of the toe; therefore any method of securing the toe sensor whichemploys fastenings around the toe could compress the arteries and veins,spoiling the effects of the postural test. This is especially importantif a vasodilatory response is to be observed as these mechanical effectswould mask the homeostasis response.

In addition, adhesive pads may be located at strategic points along theflexible substrate to stabilize the substrate and reduce sensor movementand resultant motion artifact.

The flexible substrate 62 illustrated in FIG. 5B can with minormodification be made suitable for use with a hand. The reflectancesensor is located on the back of the hand and the transmission sensor islocated on the index finger.

An alternative embodiment of this flexible substrate sensor would employsensor elements on both sides of the substrate, permitting the substrateto be utilized on either foot.

Handedness Detection

A connecting cable connects with the edge conductor 74. The connectingcable has a series of contacts which are connected (perhapssemi-permanently) through the cable to particular parts of the front endcircuitry 32. Consequently, the arrangement of the contacts at theinterface of the connecting cable has, at least initially, a specific,predefined dedicated order. Thus a dedicated contact is always used toenergize a first sensor and a dedicated contact is always used toreceive.

Thus for example the following simplified table may illustrate a firstcorrespondence between the contacts of the cable and those of the edgeconnector.

TABLE 1 Cable Contact Connector Contact 1 Output LED 1 Sensor 1 2 InputLED 2 Sensor 1 3 Output LED 3 Sensor 2 4 Input LED 4 Sensor 2

The following simplified table may illustrate a second correspondencebetween the contacts of the cable and those of the edge connector.

TABLE 2 Cable Contact Connector Contact 1 Output LED 1 Sensor 1 2 InputLED 2 Sensor 2 3 Output LED 3 Sensor 2 4 Input LED 4 Sensor 1

It is possible for the front end circuitry 32 to determine which ofthese configurations is used by applying an output LED control signal ononly cable contact 1. If an input is received at the front end circuitry32 on connector contact 2 then the first configuration is in use whereasif an input is received at the front end circuitry 32 on connectorcontact 4 then the second configuration is in use.

The different configurations may be used to identify differentsubstrates 62.

Alternatively, the same substrate may be reversible with the firstconfiguration used on one side and the second configuration used on theother side. This would enable the front end circuitry to determine thehandedness of the substrate i.e. whether it is applied to a left orright foot. The front-end circuitry may then for example change how itprovides signals to the substrate and how it interprets signals from thesubstrate.

It would also be possible to add redundant and/or degenerate contacts tocreate different configurations.

It is therefore possible to have a collection of flexible substrateswhere each substrate is ergonomically configured to be applied to adifferent body part of a subject. Each substrate may comprise the same(or different) sensors and will have a set of interconnects supported bythe flexible substrate that connect to the sensors. Each substrate willalso have an interface comprising a common fixed physical configurationof interface connectors (connector contacts) for connecting theinterconnects to remote processing circuitry via the cable. An orderingof the interconnects with respect to the common fixed physicalconfiguration of interface connectors is dependent upon the body part towhich a flexible substrate is to be applied. The ordering of theinterconnects with respect to the common fixed physical configuration ofinterface connectors is uniquely indicative, when the flexible substrateis in use, to the processing circuitry of the body part to which theflexible substrate is attached.

Safety Control

Referring to FIGS. 5A, 5B and 5C, the flexible substrate 62 may have ascore or partial cut 90 (kiss-cut) through close to the designated edgeconnector 74. The width of the score may be across the whole of a tabsupporting the edge connector 74 or more typically across 90% the width,leaving some of the substrate un-scored. The scoring produces alocalized structural weakness controlled by the depth of the score, thecross section of the substrate and the tensile strength of the substratematerial.

The interconnects 80 connecting the edge connector 74 to sensors may beformed from conductive ink, the thickness of the ink is tightlycontrolled, so the cross sectional area is less in the width of thescore, but still sufficient to carry the appropriate current.

The design of the connecting cable's distal end female edge connector 94includes a spring loaded retainer 92 which engages with a notch 83 onthe side of the substrate male edge connector 74, or alternatively thecable edge connector includes a spring loaded detent pin which engageswith a hole in the substrate close to the exposed edges of the connectortab. These features are designed into an edge connector shroud and areinaccessible by the user. The preferred method would use a small sectionof Printed Circuit Board (PCB) as a chassis, with the edge connectormounted and soldered to the PCB with through hole pins, where a piece ofspring steel formed to act as the retaining lever is also soldered tothe PCB. The cable shroud then serves to protect and form a substantial,rigid enclosure which can accept the force of the retainer and force ofthe operator.

When the kinematic test is complete, the operator removes the substrate62 from the subject in the conventional way. The sensor is removed fromthe subject as normal, but for the substrate 62 to be removed from thecable edge connector, the substrate must be firmly grasped and pulled inorder to overcome the spring loaded retainer 92 located in the edgerconnector shroud. At this moment the substrate section with the scorewill break, fracturing the interconnects 80. The score 90 runstransversely across some or all of the interconnects 80.

As the substrate is only partially scored, a section of the substratewill still remain intact, holding the tab to the remaining substrate.This prevents the substrate from breaking into two and the edgeconnector tab from getting stuck in the female edge connector.

To further facilitate this, the substrate is formed as a laminate of twolayers 81A and 81B that are folded about join 83 and adhered together(FIG. 5A). Less or no adhesive glue is applied between the layers wherethe layer 81A has a score 90. In this embodiment, the score is made onlyin the laminate layer 81A supporting the interconnects. The portion ofthis laminate layer 81A demarcated by the score breaks away and maydetach (FIG. 5C). The retainer is however now no longer in effect, andthe retained portion may be easily removed from the female edgeconnector.

The other laminated layer 81B underlying the detachable portion 87 ofthe laminate layer 81A may be colored 89 e.g. red. When the portion 87of the laminate layer 81A detaches severing the interconnects 90, theunderlying colored layer 89 is exposed. This would indicate to the userthat the substrate 62 has been used and should be disposed.

This method of fracturing the conductive ink conductors is far superiorto the accidental, possibly intermittent, fractured conductor producedby material fatigue reuse, since the proposed method for producing thefractured electrical conductor is defined and reliable. Attempting toreuse a substrate with fractured conductors would be detected by thefront end circuitry 32 when it performs the standard self tests wheninitializing for a kinematic test. For example, detecting insufficientpower being consumed by the LEDs indicates fracture in the LED conductorlines.

For additional security, a programmable component such as a fusible linkmay also be incorporated as part of the conductive ink inside thesensor, which permits a sensor to be marked as ‘used’ by the systemafter the test. The fusible link can be effected by carefullycontrolling the screen printing process to deliver a conductive inksection with a known cross sectional area for a given maximum powerdissipation. A short electrical pulse substantially exceeding thismaximum power dissipation would controllably disrupt the fusible link,leaving it open circuit. The fusible link would be brought out to anadditional edge connector conductor, or would be part of the existingtracking inside the sensor.

The blocks illustrated in the Figs may represent steps in a methodand/or sections of code in the computer program. The illustration of aparticular order to the blocks does not necessarily imply that there isa required or preferred order for the blocks and the order andarrangement of the block may be varied. Furthermore, it may be possiblefor some steps to be omitted.

Although embodiments of the present invention have been described in thepreceding paragraphs with reference to various examples, it should beappreciated that modifications to the examples given can be made withoutdeparting from the scope of the invention as claimed.

Features described in the preceding description may be used incombinations other than the combinations explicitly described.

Although functions have been described with reference to certainfeatures, those functions may be performable by other features whetherdescribed or not.

Although features have been described with reference to certainembodiments, those features may also be present in other embodimentswhether described or not.

Whilst endeavoring in the foregoing specification to draw attention tothose features of the invention believed to be of particular importanceit should be understood that the Applicant claims protection in respectof any patentable feature or combination of features hereinbeforereferred to and/or shown in the drawings whether or not particularemphasis has been placed thereon.

I/We claim: 1-35. (canceled)
 36. An apparatus comprising: an inputinterface configured to provide signals from at least two sensors for atleast two postures including: signals, dependent upon blood presence,from a first sensor when a subject is in a first posture; signals,dependent upon blood presence, from the first sensor when the subject isin a second posture; signals, dependent upon blood presence, from asecond sensor when the subject is in the first posture; and signals,dependent upon blood presence from the second sensor when the subject isin the second posture; and processing circuitry configured to determineand output a metric by combining, according to pre-defined calibrationdata the provided signals.
 37. An apparatus as claimed in claim 36,wherein the provided signals, for each combination of sensor andposture, comprises at least one logarithm of detected light intensity.38. An apparatus as claimed in claim 36, wherein the signals, for eachcombination of sensor and posture, include a time varying component ofdetected light intensity and a separated quasi static component ofdetected light intensity.
 39. An apparatus as claimed in claim 36,wherein the signals, for each combination of sensor and posture, includeseparately a logarithm of a time varying component of detected lightintensity and a logarithm of a quasi static component of the detectedlight intensity.
 40. An apparatus as claimed in claim 36, wherein thesignals, for each combination of sensor and posture, include a signalbased upon a light intensity signal detected at an optical reflectancesensor and a signal based upon a light intensity signal detected at anoptical transmission sensor.
 41. An apparatus as claimed in claim 36,wherein the signals, for each combination of sensor and posture, includea signal based upon a light intensity signal detected at a firstwavelength but not at a second wavelength and a signal based upon alight intensity signal detected at, at least, the second wavelength butnot the first wavelength.
 42. An apparatus as claimed in claim 36,wherein the calibration data is used to assess divergence of theprovided signals from an expected average of a statistical model ofexpected signals to produce the metric, wherein the provided signalscomprise signals that have been statistically manipulated to be averagedsignals.
 43. An apparatus as claimed in claim 36, wherein thecalibration data is predetermined using machine learning.
 44. Anapparatus as claimed in claim 36, configured to emulate an artificialneural network comprising a plurality of nodes each of which hasassociated weights for inputs to the node, wherein the calibration dataprovides said weights and wherein the artificial neural network receivesas inputs the provided signals wherein the provided signals comprisesignals that have been statistically manipulated to be averaged signals.45. An apparatus as claimed in claim 36, further comprising a memorystoring multiple sets of calibration data comprising a set ofcalibration data for each of a plurality of predetermined standardsequences of different body postures, wherein the processing circuitryis configured to determine and output a metric for a particularpredetermined standard sequence of different body postures by combining,according to calibration data for the particular predetermined standardsequence of different body postures, the provided signals.
 46. Anapparatus as claimed in claim 36, wherein at least one of the sensorsprovide signals from optical reflection detectors.
 47. An apparatus asclaimed in claim 36, wherein at least the first sensor is configured tobe placed on the limb.
 48. An apparatus as claimed in claim 36, whereinat least the first sensor is configured to be placed on the subject'shead.
 49. An apparatus as claimed in claim 48, wherein the first sensorprovides signals from an optical transmission sensor.
 50. An apparatusas claimed in claim 36, wherein the calibration data is used to assess adivergence of the provided signals from an expected pattern of signalsthat characterize an expected response of a normalized circulationsystem to the predetermined sequence of first, second and thirdpostures.
 51. An apparatus as claimed in claim 36, wherein theprocessing circuitry is configured to perform pattern matching betweenpatterns produced by the provided signals during a kinematic protocolinvolving at least a change between first, second and third postures andnormal circulatory response patterns.
 52. An apparatus as claimed inclaim 51, wherein the weightings are determined by training.
 53. Anapparatus as claimed in claim 36, wherein the processing circuitry isconfigured to combine, according to pre-defined calibration data theprovided signals, by using summation and weightings.
 54. A systemcomprising: at least a first sensor and a second sensor; and anapparatus comprising: an input interface configured to provide signalsfrom at least the first sensor and the second sensor for at least twopostures including: signals, dependent upon blood presence, from thefirst sensor when a subject is in a first posture; signals, dependentupon blood presence, from the first sensor when the subject is in asecond posture; signals, dependent upon blood presence, from the secondsensor when the subject is in the first posture; and signals, dependentupon blood presence from the second sensor when the subject is in thesecond posture; and processing circuitry configured to determine andoutput a metric by combining, according to pre-defined calibration datathe provided signals.
 55. A system as claimed in claim 54, wherein thefirst sensor is at a first location and the second sensor is at asecond, different, location.
 56. A system as claimed in claim 54,wherein the first sensor detects light at a first wavelength but not ata second wavelength and the second sensor detects light at the secondwavelength but not at the first wavelength.
 57. A system as claimed inclaim 54, wherein the first sensor is a reflectance sensor and isattached without clamping using an opaque adhesive collar that closelycircumscribes the reflectance sensor.
 58. A system as claimed in claim54, wherein the first sensor and second sensor are attached to aflexible substrate comprising interconnects that are connectable to theapparatus via an interface, wherein a portion of the flexible substrate,underlying one or more of the interconnects, has a manufacturedstructural weakness and wherein, in use, the portion of the flexiblesubstrate having the structural weakness connects with the interfacewhich retains the substrate against removal such that on attemptedremoval of the flexible substrate from the interface the manufacturedstructural weakness breaks the one or more interconnects.
 59. A systemas claimed in claim 58, wherein the interface additionally detaches aportion of the flexible substrate to reveal an indicator.
 60. A systemas claimed in claim 54, wherein the first sensor and second sensor areattached to a flexible substrate for application to a subject and areconnectable to the processing circuitry via a first set of interconnectsembedded in the flexible substrate, wherein an ordering of theinterconnects embedded in the substrate is dependent upon whether theflexible substrate is for use on a right limb or a left limb and whereinthe ordering of the interconnects embedded in the substrate, in use, isindicative to the processing circuitry of whether the flexible substrateis applied to a right limb of the subject or a left limb of the subject.61. A system as claimed in claim 54, wherein the first sensor and secondsensor are attached to a first side of a flexible reversible substrateand are connectable to the processing circuitry via a first set ofinterconnects on the first side of the flexible substrate and wherein athird sensor and a fourth sensor are attached to a second side of theflexible substrate and are connectable to the processing circuitry via asecond set of interconnects on the second side of the flexiblesubstrate, wherein an ordering of the first set of interconnects acrossthe first side of the flexible interconnect, when the first side of theflexible substrate is upwards facing, is different to an ordering of thesecond set of interconnects across the first side of the flexiblesubstrate when the second side of the flexible substrate is upwardsfacing thereby enabling the processing circuitry to determine which sideof the reversible flexible substrate is operational.
 62. A system asclaimed in claim 54, wherein first signals detected by the first sensorare processed to produce parallel signals that have different frequencycomponents before combination at the processing circuitry and whereinsecond signals detected by the second sensor are processed to produceparallel signals that have different frequency components beforecombination by the processing circuitry.
 63. A method comprising:attaching at least a first optical sensor and a second optical sensorsto a subject; and connecting the optical sensors to an apparatuscomprising: an input interface configured to provide signals from atleast the first sensor and the second sensor for at least two posturesincluding: signals, dependent upon blood presence, from the first sensorwhen a subject is in a first posture; signals, dependent upon bloodpresence, from the first sensor when the subject is in a second posture;signals, dependent upon blood presence, from the second sensor when thesubject is in the first posture; and signals, dependent upon bloodpresence from the second sensor when the subject is in the secondposture; and processing circuitry configured to determine and output ametric by combining, according to pre-defined calibration data theprovided signals; and moving the subject through a predetermined orderedsequence of different postures including the first and second postures.64. A method as claimed in claim 63, wherein the optical sensors areattached by attaching a disposable flexible substrate to the subject.65. A method as claimed in claim 64, wherein the disposable flexiblesubstrate is attached to a limb and comprises at least one opticalreflectance sensor.
 66. A method as claimed in claim 65, wherein theflexible substrate is attached using adhesive only and without the useof a clamping force.
 67. A method as claimed in claim 63, wherein thedisposable flexible substrate is attached to a subject's head andcomprises at least one optical transmission sensor.
 68. A method asclaimed in claim 63, wherein moving the subject through a predeterminedordered sequence of different postures comprises moving the subjectbetween postures to cause a local, as opposed to systemic, circulatoryreaction.
 69. A method as claimed in claim 63, wherein moving thesubject through a predetermined ordered sequence of different posturescomprises moving the subject between postured to cause, for the subject,a relative vertical displacement with respect to the subject's heart ofa subject's peripheral limb without relative vertical displacement withrespect to the subject's heart of the subject's head.
 70. A method asclaimed in claim 63, wherein moving the subject through a predeterminedordered sequence of different postures comprises moving the subjectbetween postured to cause a systemic circulatory reaction.
 71. A methodas claimed in claim 63, wherein moving the subject through apredetermined ordered sequence of different postures comprises movingthe subject between postures to cause, for the subject, a relativevertical displacement, with respect to the subject's heart, of thesubject's head.
 72. A method as claimed in claim 63, moving the subjectthrough a predetermined ordered sequence of different postures includingthe first, the second posture and a third posture.